CLU: Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins. Prevents stress- induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. Belongs to the clusterin family. 5 isoforms of the human protein are produced by alternative splicing.
Protein type: Mitochondrial; Secreted; Secreted, signal peptide; Apoptosis
Chromosomal Location of Human Ortholog: 8p21-p12
Cellular Component: cell surface; cytoplasm; cytosol; endoplasmic reticulum; extracellular matrix; extracellular region; extracellular space; Golgi apparatus; growth cone; intracellular; mitochondrial membrane; mitochondrion; nucleus; perinuclear region of cytoplasm; protein complex
Molecular Function: ATPase activity; chaperone binding; misfolded protein binding; protein binding; protein N-terminus binding; ubiquitin protein ligase binding
Biological Process: activation of NF-kappaB transcription factor; aging; blood coagulation; cell morphogenesis; chaperone-mediated protein complex assembly; complement activation; complement activation, classical pathway; endocrine pancreas development; innate immune response; lipid metabolic process; microglial cell activation; myelin maintenance in the central nervous system; negative regulation of protein homooligomerization; neurite morphogenesis; platelet activation; platelet degranulation; positive regulation of apoptosis; positive regulation of cell differentiation; positive regulation of cell proliferation; positive regulation of nitric oxide biosynthetic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of tumor necrosis factor production; protein import; protein stabilization; release of cytochrome c from mitochondria; response to light stimulus; response to misfolded protein; response to virus; reverse cholesterol transport
Show more